Resolution of sickle cell disease-associated inflammation and tissue damage with 17R-resolvin D1.
Blood
; 133(3): 252-265, 2019 01 17.
Article
en En
| MEDLINE
| ID: mdl-30404812
ABSTRACT
Resolvins (Rvs), endogenous lipid mediators, play a key role in the resolution of inflammation. Sickle cell disease (SCD), a genetic disorder of hemoglobin, is characterized by inflammatory and vaso-occlusive pathologies. We document altered proresolving events following hypoxia/reperfusion in humanized SCD mice. We demonstrate novel protective actions of 17R-resolvin D1 (17R-RvD1; 7S, 8R, 17R-trihydroxy-4Z, 9E, 11E, 13Z, 15E, 19Z-docosahexaenoic acid) in reducing ex vivo human SCD blood leukocyte recruitment by microvascular endothelial cells and in vivo neutrophil adhesion and transmigration. In SCD mice exposed to hypoxia/reoxygenation, oral administration of 17R -RvD1 reduces systemic/local inflammation and vascular dysfunction in lung and kidney. The mechanism of action of 17R-RvD1 involves (1) enhancement of SCD erythrocytes and polymorphonuclear leukocyte efferocytosis, (2) blunting of NF-κB activation, and (3) a reduction in inflammatory cytokines, vascular activation markers, and E-selectin expression. Thus, 17R-RvD1 might represent a new therapeutic strategy for the inflammatory vasculopathy of SCD.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neumonía
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Antiinflamatorios no Esteroideos
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Ácidos Docosahexaenoicos
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Anemia de Células Falciformes
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Enfermedades Renales
Tipo de estudio:
Etiology_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article